Simplicity’s Virtue Scorned

Utilization of a simple method for the angiographic characterization of coronary flow after thrombolytic therapy for myocardial infarction has become a hallmark of research efforts in this field since its introduction by the TIMI (Thrombolysis In Myocardial Infarction) investigators in 1985.1 TIMI flow grades 0 (no flow), 1 (minimal flow), 2 (partial flow), or 3 (complete flow) are now an integral part of the unique vocabulary of cardiologists the world over. This flow characterization has the virtue of being as accessible as the nearest video monitor or cineangiographic viewer and can be obtained quickly, at no additional cost. TIMI flow measurements have appeared to be extremely useful as prognostic indicators of the long-term success or failure of thrombolysis,2 to risk-stratify patients,3 and to compare the efficacy of various thrombolytic regimens.4 Since large mortality trials are expensive and difficult to perform, the 90-minute TIMI flow grade often has been used as a surrogate end point. Early investigators subdivided patients into two groups: TIMI flow grades 0 and 1 at 90 minutes (an undesirable outcome) and TIMI flow grades 2 and 3 (a favorable outcome). More recent investigators have shown considerable differences in the clinical results achieved between TIMI flow grades 2 and 3. A retrospective analysis of four German multicenter thrombolytic trials by Vogt et al5 showed that only patients achieving TIMI flow grade 3 after thrombolysis fared better than TIMI grades 0 and 1. Similar outcomes were obtained by the TEAM-2 investigators, who found that only TIMI flow grade 3 resulted in an improved outcome after thrombolysis.6 Patients achieving TIMI grade 2 flow followed the same course as grades 0 and 1. Although widely used, the validity, reproducibility, and determinants of TIMI flow measurements have, unfortunately, received little attention. Most investigators, apparently convinced by …